Project Summary The aim of this project is to develop mucus-penetrating particles (MPP) that will improve microbicide delivery for protection against HIV and other STD pathogens such as HSV. The aim of the R21 phase is to develop MPP to be tested in the R33 phase for protection against HIV in the humanized-BLT-SGlD mouse model. We have completed all of our negotiated milestones. Additionally, we present significant data that support our hypothesis that biodegradable MPP will provide improved protection against HIV and HSV when delivered vaginally once-a-day (non-coitally). We currently have biodegradable MPP that are ready for testing against HSV in our mouse model and against HIV in the humanized-BLT-SClD mouse model in the R33 phase of this project.